COVID-19 severity associates with pulmonary redistribution of CD1c+ DCs and inflammatory transitional and nonclassical monocytes
Ildefonso Sánchez-Cerrillo, … , Enrique Martín-Gayo, the REINMUN-COVID and EDEPIMIC groups
Ildefonso Sánchez-Cerrillo, … , Enrique Martín-Gayo, the REINMUN-COVID and EDEPIMIC groups
Published August 12, 2020
Citation Information: J Clin Invest. 2020;130(12):6290-6300. https://doi.org/10.1172/JCI140335.
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Research Article Immunology

COVID-19 severity associates with pulmonary redistribution of CD1c+ DCs and inflammatory transitional and nonclassical monocytes

Abstract

SARS-CoV-2 is responsible for the development of coronavirus disease 2019 (COVID-19) in infected individuals, who can either exhibit mild symptoms or progress toward a life-threatening acute respiratory distress syndrome (ARDS). Exacerbated inflammation and dysregulated immune responses involving T and myeloid cells occur in COVID-19 patients with severe clinical progression. However, the differential contribution of specific subsets of dendritic cells and monocytes to ARDS is still poorly understood. In addition, the role of CD8+ T cells present in the lung of COVID-19 patients and relevant for viral control has not been characterized. Here, we have studied the frequencies and activation profiles of dendritic cells and monocytes present in the blood and lung of COVID-19 patients with different clinical severity in comparison with healthy individuals. Furthermore, these subpopulations and their association with antiviral effector CD8+ T cell subsets were also characterized in lung infiltrates from critical COVID-19 patients. Our results indicate that inflammatory transitional and nonclassical monocytes and CD1c+ conventional dendritic cells preferentially migrate from blood to lungs in patients with severe COVID-19. Thus, this study increases the knowledge of specific myeloid subsets involved in the pathogenesis of COVID-19 disease and could be useful for the design of therapeutic strategies for fighting SARS-CoV-2 infection.

Authors

Ildefonso Sánchez-Cerrillo, Pedro Landete, Beatriz Aldave, Santiago Sánchez-Alonso, Ana Sánchez-Azofra, Ana Marcos-Jiménez, Elena Ávalos, Ana Alcaraz-Serna, Ignacio de los Santos, Tamara Mateu-Albero, Laura Esparcia, Celia López-Sanz, Pedro Martínez-Fleta, Ligia Gabrie, Luciana del Campo Guerola, Hortensia de la Fuente, María J. Calzada, Isidoro González-Álvaro, Arantzazu Alfranca, Francisco Sánchez-Madrid, Cecilia Muñoz-Calleja, Joan B. Soriano, Julio Ancochea, Enrique Martín-Gayo, the REINMUN-COVID and EDEPIMIC groups

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Figure 1

t-SNE visualization of cell subset distribution in the blood of COVID-19 patients.

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t-SNE visualization of cell subset distribution in the blood of COVID-19...
(A) t-SNE analysis of myeloid cells from a total of 49 samples (34 COVID-19 patients and 15 non–COVID-19 [NC] controls) gated after exclusion of lineage-positive cells and excluding granulocytes. Upper dot plots on the left show combined density of cell clusters in both patient groups. Lower dot plots on the right display highlighted distribution of each indicated myeloid cell population. Cell populations present in both t-SNE plots are highlighted with a number. Those populations changing in the 2 patient groups are highlighted in red. (B) Quantification of numbered cell populations identified by t-SNE in A from the blood of COVID-19 and NC controls. Statistical significance was calculated using χ2 test and FDR multiple-comparison correction. *P < 0.05; **P < 0.01; ***P < 0.001.